|
【结 构 式】 
|
【分子编号】13495 【品名】3-Chloro-6-methylpyridazine 【CA登记号】1121-79-5 |
【 分 子 式 】C5H5ClN2 【 分 子 量 】128.56088 【元素组成】C 46.71% H 3.92% Cl 27.58% N 21.79% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 2-(1-benzylpiperidin-4-yl)ethanol (I) with 4-hydroxybenzoic acid ethyl ester (II) by means of triphenylphosphine and diazenedicarboxylic acid diethyl ester in THF gives 4-[2-(1-benzylpiperidin-4-yl)ethoxy]benzoic acid ethyl ester (III) as fumarate salt. This compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol, yielding the free product (IV), which is finally condensed with 3-chloro-6-methylpyridazine (V) by means of K2CO3 in DMF.
| 【1】 Stokbroekx, R.A.; Van der Aa, M.J.M.; Luyckx, M.G.M.; Grauwels, G.A.J. (Janssen Pharmaceutica NV); Novel pyridazinamine derivs. AU 8825751; EP 0320032; JP 1989207278; US 4992433 . |
| 【2】 Castaner, J.; Prous, J.; Pirodavir. Drugs Fut 1992, 17, 11, 997. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 13491 | N-Benzyl-4-(2-hydroxyethyl)piperidine; 2-(1-Benzyl-4-piperidinyl)-1-ethanol | 76876-70-5 | C14H21NO | 详情 | 详情 |
| (II) | 13492 | ethyl p-hydroxybenzoate; ethyl 4-hydroxybenzoate | 120-47-8 | C9H10O3 | 详情 | 详情 |
| (III) | 13493 | ethyl 4-[2-(1-benzyl-4-piperidinyl)ethoxy]benzoate | C23H29NO3 | 详情 | 详情 | |
| (IV) | 13494 | ethyl 4-[2-(4-piperidinyl)ethoxy]benzoate | C16H23NO3 | 详情 | 详情 | |
| (V) | 13495 | 3-Chloro-6-methylpyridazine | 1121-79-5 | C5H5ClN2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Treatment of 3-chloro-6-methylpyridazine (I) with thionyl chloride followed by reaction with imino derivative (II) in CH2Cl2 provides thiadiazolyl pyridazine derivative (III), which is then condensed with amine (IV) in the presence of Na2CO3 in DMF.
| 【1】 Stokbroekx, R.A.; Van der Aa, M.J.M.; Willems, M.; Meerpoel, L.; Luyckx, M.G.M.; Tuman, R.W. (Janssen Pharmaceutica NV); Angiogenesis inhibiting pyridazinamines. EP 0876366; JP 2000503014; US 5985878; WO 9726258 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 13495 | 3-Chloro-6-methylpyridazine | 1121-79-5 | C5H5ClN2 | 详情 | 详情 |
| (II) | 15369 | Iminoformamide; Methanimidamide | 463-52-5 | CH4N2 | 详情 | 详情 |
| (III) | 47583 | 3-chloro-6-(1,2,4-thiadiazol-5-yl)pyridazine | C6H3ClN4S | 详情 | 详情 | |
| (IV) | 47584 | N-(4-piperidinyl)-N-[3-(trifluoromethyl)phenyl]amine; N-[3-(trifluoromethyl)phenyl]-4-piperidinamine | C12H15F3N2 | 详情 | 详情 |